The present invention relates to the examination of tissues for indications of disease therein.
Breast, ovarian and cervical cancers are serious diseases that affect over 193,000 women per year. Hence, early detection and treatment of such cancers are important. It is well known that mammographic screening is a key tool in the early detection of breast cancers and that the early detection of breast cancer can reduce the likelihood of death caused by breast cancer. One limitation to the utility of mammography is that benign and malignant lesions oftentimes have similar morphology and are difficult to distinguish based solely on the results of a mammogram. Ovarian cancers are hard to diagnose. Consequently, biopsy is often the only certain way to distinguish between benign and malignant tumors. Biopsy is a surgical procedure performed in a hospital and, hence, is tedious, time-consuming, and expensive. Moreover, most biopsied tumors are found to be benign. Consequently, it is often difficult to determine whether the correct specimen is being biopsied unless the specimen includes a visible lesion.
Therefore, there is clearly a need for a real-time technique for examining tissues and organs in situ without first requiring that a biopsy be performed thereon to correctly identify particular tissues of interest within an organ or on the surface of mucosa.
Optical spectroscopy may play an important role in such an examination technique and may be used to monitor tissue changes before, during and after chemotherapy and/or radiation therapy. For example, native fluorescence spectroscopy and Raman spectroscopy offer new possible methods for detection and characterization of physical, chemical and structural changes in diseased tissue, for either in vivo or in vitro applications of the mucosa layers.
In U.S. Pat. No. 5,131,398 to Alfano et al., which issued Jul. 21, 1992 and which is incorporated herein by reference, there is disclosed a method and apparatus for distinguishing cancerous tumors and tissue from benign tumors and tissue or normal tissue using native fluorescence. The mucosa tissue surface to be examined is excited with a beam of monochromatic light at 300 nanometers (nm). The intensity of the native fluorescence emitted from the tissue is measured at, for example, 340 and 440 nm. The ratio of the two intensities is then calculated and used as a basis for determining if the tissue is cancerous as opposed to benign or normal. The patent is based on the discovery that when tissue is excited with monochromatic light at 300 nm, the native fluorescence spectrum over the region from about 320 nm to 600 nm is substantially different for cancerous tissue than for benign tumors and tissue or normal tissue.
In U.S. Pat. No. 5,261,410 to Alfano et al., which issued Nov. 16, 1993 and which is incorporated herein by reference, there is disclosed a method for determining if a tissue is a malignant tumor tissue, a benign tumor tissue, or a normal or benign tissue. The method is based on the discovery that, when irradiated with a beam of infrared, monochromatic light, malignant tumor tissue, benign tumor tissue, and normal or benign tissue produce distinguishable Raman spectra. For human breast tissue, some salient differences in the respective Raman spectra are the presence of four Raman bands at a Raman shift of about 1078, 1300, 1445 and 1651 cm.sup.-1 for normal or benign tissue, the presence of three Raman bands at a Raman shift of about 1240, 1445 and 1659 cm.sup.-1 for benign tumor tissue, and the presence of two Raman bands at a Raman shift of about 445 and 1651 cm.sup.-1 for malignant tumor tissue. In addition, it was discovered that for human breast tissue the ratio of intensities of the Raman bands at a Raman shift of about 1445 and 1659 cm.sup.-1 is about 1.25 for normal or benign tissue, about 0.93 for benign tumor tissue, and about 0.87 for malignant tumor tissue.
The above-described methods rely on emissions from the surfaces of photoexcited mucosa.